Characterization of Mayven, a novel actin-binding protein predominantly expressed in brain

The cytoskeleton plays an important role in neuronal morphogenesis. We have identified and characterized a novel actin-binding protein, termed Mayven, predominantly expressed in brain. Mayven contains a BTB (broad complex, tr amtrack, bric-a-brac)/POZ (poxvirus, zinc finger) domain-like structure in the predicted N terminus and "kelch repeats" in the predicted C-terminal do main. Mayven shares 63% identity (77% similarity) with the Drosophila ring canal ("kelch") protein. Somatic cell-hybrid analysis indicated that the hu man Mayven gene is located on chromosome 4q21.2, whereas the murine homolog gene is located on chromosome 8. The BTB/POZ domain of Mayven can self-dim erize in vitro, which might be important for its interaction with other BTB /POZ-containing proteins. Confocal microscopic studies of endogenous Mayven protein revealed a highly dynamic localization pattern of the protein. In U373-MG astrocytoma/ glioblastoma cells, Mayven colocalized with actin fila ments in stress fibers and-in patchy cortical actin-rich regions of the cel l margins. In primary rat hippocampal neurons, Mayven is highly expressed i n the cell body and in neurite processes. Binding assays and far Western bl otting analysis demonstrated association of Mayven with actin. This associa tion is mediated through the "kelch repeats" within the C terminus of Mayve n. Depolarization of primary hippocampal neurons with KCl enhanced the asso ciation of Mayven with actin. This increased association resulted in dynami c changes in Mayven distribution from uniform to punctate localization alon g neuronal processes. These results suggest that Mayven functions as an act in-binding protein that may be translocated along axonal processes and migh t be involved in the dynamic organization of the actin cytoskeleton in brai n cells.